Low carryover liquid handling probe for an automated analyzer

ABSTRACT

Provided herein is a carryover-reducing liquid handling probe for an analytical system, incorporating a rigid sheath and a polymer core that extends from the sheath to act as the fluid contact surface.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 14/129,382, filed Apr. 3, 2014, which is a US National Stage Entryunder §371 of International Application No. PCT/US2012/044431, filedJun. 27, 2012, which claims priority to U.S. Provisional Application No.61/504,070, filed Jul. 1, 2011, the disclosures of which areincorporated by reference herein in their entirety for all purposes.

BACKGROUND

A wide variety of automated analyzers are available, performing analysesthat range from simple pH determination to sophisticated testing thatdetermines the presence of genetic markers. Despite this range offunctions and capabilities, however, nearly all automated analyzers havecommon basic functionalities and performance issues. An automatedanalyzer must manipulate patient samples, which are generally liquids,such as blood, plasma, serum, urine, cerebrospinal fluid, or saliva.Solid or semisolid samples, such as tissue samples and fecal material,can treated as a liquid following maceration and suspension in a liquid.As such samples are provided in containers, such as venous bloodcollection tubes, and are generally manipulated by aspiration from thesecontainers using one or more liquid handling probes. In order to movethese fluids and liquid reagents to different locations on an automatedanalyzer a liquid handling probe may be attached to a moving carriage.

Automated analyzers generally share a common workflow, each step ofwhich is a potential source of error that can degrade systemperformance. In a typical automated analyzer containers holding liquidsamples are first loaded into the system by the operator. A roboticliquid handling probe then removes a portion of the sample which is usedfor testing. One or more reagents, which are also generally in liquidform, are retrieved from storage using a robotic liquid handling probeand subsequently mixed with the sample in order to perform an assayreaction that generates a detectable result.

As noted above liquid transfer is a process that is performed frequentlyon automated analyzers, and is a potential source of error that maydegrade the quality of assay results. One assay characteristic that canbe severely impacted by such errors is sensitivity, which is essentiallya measure of the lowest concentration of a particular analyte that theanalyzer can reliably detect or quantify. In many instances thesensitivity of a particular assay is a function of variation in thesignal associated with a result from an assay performed on sample thatdoes not contain the analyte, also known as the background signal. Alarge amount of variation in the background signal results will limitthe sensitivity of the analyzer to concentrations of the analyte thatreturn a relatively strong signal, one that is statisticallydistinguishable from the widely varying background signal. Conversely, asmall amount of variation in the background signal can permit thedetection of relatively low concentrations or analyte that generate arelatively weak signal.

One source of variation in the background signal is carryover orcontamination. Carryover occurs when material is transferred from afirst fluid to an analyzer component and then from that analyzercomponent to a second fluid. A typical scenario is when a small volumeof fluid from a patient sample containing a very high concentration ofanalyte is transferred to a second patient sample by a liquid handlingprobe, leading to a falsely positive test result from the second sample.Similar transfers of liquid assay reagents are also possible.

Carryover can occur by physical transfer of a volume of fluid. This canoccur in crevices that are inherent in the design of the liquid handlingprobe, or may take place in irregularities in the surface of the liquidhandling probe that may occur due to rough handling or inadvertentcollisions during use. Another source of carryover is the interaction ofspecific molecules in the sample with a wetted surface of the liquidhandling probe. Once bound to such a surface these molecules maysubsequently be released when the liquid handling probe enters adifferent fluid. Carryover may also occur by a combination of thesemechanisms.

A number of approaches have been developed to minimize carryover. One ofthese is the use of disposable tips to handle fluids. These tips areapplied to the liquid handling probe mechanism prior to handling a fluidand disposed of thereafter. Supplying and manipulating these disposabletips can add significant cost and complexity to an automated analyzer,and the time required to attach and dispose of the tips can impactsystem throughput. Improper attachment of a tip to a liquid handlingprobe may also lead to delivery of inaccurate volumes that impact assayresults, and thereby become yet another source of variation.

Another approach is to implement rigorous washing procedures of theinterior and exterior of the liquid handling probe mechanism. Numerousdevices and methods for this have been disclosed, however these addsignificantly to the cost and complexity of an analyzer in the form ofthe need for additional workstations and wash reagents. In addition toimpacting system throughput, these washing steps also are an additionalsource of variation in the analyzer.

Carryover of fluid volumes can be minimized without resorting to thesemeasures by optimizing analyzer functions to reduce exposure of theliquid handling probe mechanism to the sample, for example by usingliquid level sensing to detect the surface of the sample liquid andsubsequently immerse only a small portion of the liquid handling probe.The liquid handling probe mechanism itself can be designed so as topresent a surface without features that can trap liquids. This can beaccomplished by electropolishing exposed metal surfaces and utilizingmaterials, such as stainless steel, that resist scratching. Positioningof the liquid handling probe can also be monitored to avoid collisionsthat may generate surface scratches and chips.

Carryover due to the binding of molecules to the material of the liquidhandling probe can be avoided by selecting materials with a low tendencyto interact with molecules in solution. These are typically polymers,such as polypropylene or fluoropolymers. A liquid handling probe may beconstructed entirely of these materials, however the relative lack ofstrength and rigidity can complicate mounting such devices to motionsystems and subsequent accurate positioning, particularly in a highthroughput analyzer that may be making rapid movements. In addition,since such materials are generally nonconductive they are not compatiblewith many liquid level sensing mechanisms. Low nonspecific bindingmaterials can be used as coatings over more conventional rigidmaterials, such as stainless steel. Such coatings are easily damagedthrough careless handling and accidental collision, however, generatingsurface scratches and chips in the polymer coating that can lead tosignificant fluid volume carryover.

Embodiments of the invention address these and other problems,individually and collectively.

SUMMARY

Provided herein is carryover-reducing liquid handling probe for ananalytical system, incorporating a rigid sheath and a polymer core thatextends from the sheath to act as the fluid contact surface. The polymercore can be conductive so that the extended portion can act as part of aliquid level sensor. The device may also include a shock absorbing mountthat simplifies user replacement of the liquid handling probe and helpsminimize damage during use. The shock absorbing mount can incorporatesensors that detect collisions, and signal the analytical system to takefurther steps that reduce damage to the liquid handling probe.

Provided herein is a liquid handling probe (or fluid handling probe)comprising an elongated rigid sheath with a distal (or lower) terminus;a conductive polymer core that is at least partially enclosed withinsaid elongated rigid sheath, said conductive polymer core including aninternal fluid conduit and a conductive polymer tip; and a liquid levelsensing mechanism operably connected to the conductive polymer core. Insome embodiments, said conductive polymer tip comprises a portion of theconductive polymer core that protrudes from the distal terminus of theelongated rigid sheath. In some embodiments, the conductive polymer coreextends beyond the distal end of the elongated rigid sheath at least0.05 inch, e.g., 0.1 inch, 0.25 inch, 0.5 inch, 0.75 inch, 1 inch,0.05-2 inch, 0.1-1 inch, 0.1-0.5 inch, etc. In some embodiments, theelongated rigid sheath has a proximal (or upper) terminus. In someembodiments, the conductive polymer core protrudes from the proximalterminus to form a flared fitting.

In some embodiments, the elongated rigid sheath comprises stainlesssteel, e.g., electropolished stainless steel. In some embodiments, theelongated rigid sheath is conductive, and the conductive polymer core isin electrical contact with said elongated rigid sheath. In someembodiments, the fluid sensing mechanism is a capacitance based liquidsensing circuit. In some embodiments, the conductive polymer corecomprises a conductive polymer with a bulk resistivity of less than 0.5Ω*m, e.g., 0.4, 0.3., 0.25, 0.1, 0.05, 0.1-0.5, or 0.2-0.4 Ω*m. In someembodiments, the conductive polymer core comprises a conductivefluoropolymer. In some embodiments, the conductive polymer corecomprises a polymer with low nonspecific binding.

Further provided is a device for handling liquids on an automatedchemistry analyzer, said automated chemical analyzer having one or morecrane assemblies, comprising (1) a liquid handling probe, e.g., any ofthe liquid handling probes embodiments described above; (2) a probemount for securing said liquid handling probe to a crane assembly of theautomated chemistry analyzer; and (3) a probe guide attached to saidprobe mount (e.g., via a probe mounting bracket). In some embodiments, apliant member is interposed between the probe mount and said probeguide. In some embodiments, the liquid handling probe is affixed to theprobe guide. In some embodiments, the device further comprises acollision detection sensor that is operably connected to the pliantmember. In some embodiments, the liquid level sensing mechanism isoperably connected to the conductive polymer core through the probeguide. In some embodiments, the liquid handling probe comprises a liquidlevel sensing mechanism operably connected to the conductive polymercore. In some embodiments, the liquid level sensing mechanism isoperably connected to the conductive polymer core through the probeguide.

Further provided is a system or method for minimizing collision damageto a liquid handling probe, comprising: a liquid handling probe affixeda probe guide, said probe guide attached to a probe mount with a pliantmember interposed between the probe guide and said probe mount, whereincollision between an object and the liquid handling probe results indisplacement of the probe guide, and distortion of said pliant member,wherein said distortion of said pliant member reduces force generatedbetween said object and said liquid handling probe during the collision.In some embodiments, distortion of said pliant member activates acollision detection sensor that then generates a signal received by acontroller. In some embodiments, the controller alters the trajectory ofthe liquid handling probe following reception of the signal from thecollision detection sensor. In some embodiments, the collision detectionsensor has an optical path. In some embodiments, distortion of thepliant member causes an opaque flag to move through the optical path ofthe collision detection sensor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a liquid handling probe 100 of the invention.

FIG. 2 shows a shock absorbing probe mount 200 of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Provided herein is a liquid handling probe 100 with a rigid externalsheath 106 and a polymer core 108, with reference to FIG. 1. The polymercore 108 can have an internal fluid conduit that facilitates aspirationand delivery of fluids. The use of an external rigid sheath 106 providesa secure point of attachment to a motion system of the analyzer that isused to align the liquid handling probe 100 with a fluid reservoir. Suchmotion systems include linear gantries, rotary gantries, and articulatedarms. The rigidity of the external sheath simplifies alignment of theliquid handling probe 100 by assuring that the relative position betweena point of attachment to a motion system and the terminus of the probethat contacts the fluid sample is fixed. This additionally permits theuse of system designs that incorporate liquid handling probes ofextended length. The external rigid sheath 106 may be made of anysuitably rigid material, including rigid plastic or metal. In someembodiments, the external rigid sheath is made of a conductive material.Suitable materials include, but are not limited to stainless steel,steel alloys, aluminum, copper, and copper alloys. The external rigidsheath can serve as a connection for a fluid level sensing circuit,and/or as a connection point between the fluid level sensing circuit andthe polymer core 108. The surface of the external rigid sheath can bepolished to reduce the impact of accidental immersion in liquid and toensure good electrical contact. In some embodiments, the external rigidsheath has an electropolished surface.

The polymer core 108 extends from a terminus of the external rigidsheath 106, and serves as the sole fluid contact surface. In someembodiments, the polymer core 108 is made of a material that has minimalinteractions with molecules in solution, i.e., a material with lownonspecific binding. This reduces carryover due to nonspecific bindingof molecules in a first solution and subsequent undesirable release ofthe bound molecules into a second solution. Suitable low nonspecificbinding materials include, but are not limited to, polypropylene,polyethylene, fluoropolymers, silicone materials, and copolymers.

In some embodiments, the polymer core is made of a conductive orsemiconductive polymer. Suitable conductive polymers include, but arenot limited to, polypropylene, polyethylene, fluoropolymers, silicone,and copolymers with inclusions of graphite or other conductive materialsat a density suitable to support the flow of electric current. In someembodiments, the conductive or semiconductive polymer has a bulkresistance of less than 0.25 Ω*m. In some embodiments, the polymer coreis made of a nonconductive material that has been treated to provide itwith a conductive or semiconductive coating.

Use of a conductive or semiconductive polymer core 108 allows thisportion of the liquid handling probe 100 to serve as a sensing portionof a liquid level sensing circuit. Such fluid sensing circuits, whichrely at least in part on contact of conductive material with liquid, areknown. In some embodiments, the liquid level sensing circuitincorporates the liquid handling probe 100 as a portion of a capacitor,and can be sensitive to direct contact with liquid and/or conductivesurface and proximity to a liquid or conductive surface.

The use of a liquid level sensing circuit permits the system to verifycontact with a liquid sample. Accordingly, the system can estimate thevolume of the sample based on the position of the liquid handling probe,and adapt to different sample volumes. The use of a liquid level sensingthrough the polymer core can also permit the system to control theextent to which the liquid handling probe is lowered into the liquidsample, thereby limiting the surface area exposed to the liquid sampleand minimizing potential carryover.

Conductive and semiconductive polymers are capable of conductingelectric current. Conventional metallic conductors are typically veryefficient conductors. In embodiments where the rigid external sheath 106is conductive, intimate contact between the rigid external sheath 106and the polymeric core 108 can allow the rigid external sheath 106 toserve as a connecting surface between a liquid level sensing circuit andthe polymeric core 108 of the liquid handling probe 100. Intimatecontact between the rigid external sheath 106 and the polymeric core 108can be due to pressure exerted by the external surface of the polymericcore 108 against the inner surface of the rigid external sheath 106, bythe use of an adhesive layer placed between the polymer core 108 and therigid external sheath 106, or a combination of the two. In suchapplications, the adhesive layer may be conductive or semiconductive.

A less efficient conductive polymeric core 108 limits the length overwhich it forms an effective sensor. In such cases, the rigid externalsheath 106 can extend over the majority of the surface of the liquidhandling probe 100 and approach the terminus of the probe. This is inharmony with the function of the rigid external sheath 106 to fix therelative positions between the proximal terminus 102, near where theliquid handling probe 100 is fixed to the motion carriage, and thedistal terminus 104, near where the liquid handling probe 100 contactsliquids. The point at which the polymeric core 108 exits the rigidexternal sheath 106 can act as a surface that can sequester fluid duringliquid transfer, thus in some embodiments, this region of the probe iskept away from the liquid surface. Given the present design, one ofskill will understand how to balance these opposing needs. In someembodiments the polymeric core 108 extends from about 0.25 to about 3inches from the distal terminus 104 of the liquid handling probe 100. Insome embodiments, the polymeric core 108 extends from about 0.25 toabout 0.75 inches from the distal terminus 104 of the liquid handlingprobe 100. In some embodiments, the polymeric core 108 extends about0.35 inches from the distal terminus 104 of the liquid handling probe100.

Use of a liquid level sensing circuit that incorporates the polymer core108, as described above, also allows the system to detect and correctmisalignment of the liquid handling probe 100. As noted above, a liquidlevel sensing circuit can detect the proximity of conductive surfaces.Input from such a liquid level sensing circuit can be use by the systemto halt movement of the liquid handling probe 100 prior to a collision.This advantageously prevents damage to the surface of the liquidhandling probe 100, e.g., scratches or chips, that could serve as afluid reservoir and result in carryover. In some embodiments, the systemmay utilize known conductive surfaces as reference points, e.g., tocalibrate or adjust the position of the motion carriage carrying theliquid handling probe 100. These reference points may be portions of thesystem that are located for additional purposes, or may be included inthe system solely for the purpose of alignment.

In the event of damage to the liquid handling probe despite suchprecautions, the use of a polymeric core 108 as the fluid contactsurface advantageously continues to present a low nonspecific bindingpolymer surface to the liquid, despite the presence of scratches, chips,and other imperfections. This limits potential carryover to theunintentional transfer of fluid volumes, which can in any event be dealtwith using a simple washing method to physically displace any carryoverfluid volumes.

In some embodiments, the polymeric core 108 may exit the proximal end102 of the external rigid sheath 106 to form a connection with otherportions of a pipetting assembly, which typically includes a fluid pump.In such applications, the terminus of the polymeric core 108 thatconnects to the pipetting assembly may be a flared fitting 110. In someembodiments, the flared fitting 110 is simply an expanded portion of thepolymeric core 108. This simplifies installation and replacement of theliquid handling probe 100 and advantageously provides a directconnection between pumping portions of the pipetting assembly and thefluid sample.

Further provided herein is s probe mount 200, e.g., for minimizingdamage to liquid handling probes, as exemplified in FIG. 2. The probemount 200 can be affixed to a transport carriage controlled by thesystem, and moved to different locations within the system. Transportcarriages include, but are not limited to, one, two and threedimensional gantry systems, rotary cranes, articulated arms, and othertransports suitable for the geometry of a particular system. In someembodiments, the liquid handling probe 100 can rest vertically within aprobe guide 202 that interfaces with the probe mount 200. The probeguide 202 may be any configuration that can securely hold a liquidhandling probe. Suitable configurations include hollow cylinders,channels, and shafts with multiple attachment points. In someembodiments, the probe guide 202 is a hollow cylinder. The probe guide202 may also include a feature that a user can loosen to remove a liquidhandling probe 100 or tighten to secure a liquid handling probe 100. Insome embodiments, this feature is a nut 206 located at one end of theprobe mount 200,

In order to minimize damage to a mounted liquid handling probe 100, theprobe guide 202 can be free to move within a probe guide channelincorporated into the probe mount 200. This free movement permits amounted liquid handling probe 100 to move during a collision, minimizingthe impact pressures of the collision, hence minimizing damage to theprobe. Such damage may be to the surface of the liquid handling probe100, in the form of scratching or pitting, or may involve bending orcrimping of the liquid handling probe 100. The probe guide 202 may besecured at one end of the probe guide 202 channel using a pliant orresilient connection 204. In such an embodiment, the liquid handlingprobe 100 can be returned to its proper position once a collision isresolved.

In some embodiments, the pliant or resilient connection 204 is a spring.

In some embodiments, the probe mount 200 includes a collision sensor,which detects impacts to the liquid handling probe 100 by detectingmovement of the probe guide 202. The system can thus halt furthermovement of the liquid handling probe 100 when a signal from thecollision sensor indicates that the liquid handling probe 100 has madeunintended contact. In some embodiments, the system can alter thetrajectory of the moving liquid handling probe 100 when a signal fromthe collision sensor indicates that the liquid handling probe 100 hasmade unintended (inadvertent) contact. Such an altered trajectory caninclude reversing the direction of movement. For example, if a liquidhandling probe 100 held by a probe mount 200 equipped with a collisionsensor encounters a solid object while moving downwards the collisionsensor will provide a signal to the system. Subsequently the system maydirect the transport carriage to which the probe mount 200 is affixed tohalt further movement, thereby minimizing damage to the liquid handlingprobe 100. In some embodiments, the system can direct the transportcarriage to which the probe mount 200 is affixed to move upwards.Intervention by the system can minimize damage to a liquid handlingprobe 100 by reducing the force and duration of impact. In addition totaking steps to minimize damage to the liquid handling probe 100, thesystem can notify the user after receiving a signal indicating that acollision has occurred.

There are a number of suitable mechanisms for sensing collision bymovement of the probe guide 202, including the use of an optical sensor,Hall effect sensor, or other position-dependent sensor that isoperatively connected to the probe guide 202. In some embodiments, thecollision sensor is an optical sensor 208 used in combination with apositional flag 210. The positional flag 210 can be mounted on the probeguide 202 and the optical sensor incorporated into the probe mount 200.Alternatively, the optical sensor 208 can be incorporated into the probeguide 202 and the positional flag 210 attached to the probe mount 200.

The probe mount 200 can also serve as a point for connection to a liquidlevel sensing circuit in instance where the liquid handling probe 100forms part of the liquid level sensing circuit. In some embodiments, theprobe mount 200 provides a fitting for attachment of a conductiveportion of a liquid handling probe 100. In some embodiments, the probeguide itself provides a connection to the liquid level sensing circuit.This simplifies attachment or replacement of a liquid handling probe 100that incorporates liquid level sensing features by integrating the actsof physically attaching the liquid handling probe 100 to the system andmaking a connection to the liquid level sensing circuit.

In some embodiments, the liquid level sensing circuit can detectproximity to conductive surfaces. In such an embodiment, the liquidlevel sensing circuit can be used in conjunction with the liquidhandling probe as described above to provide a signal to the controlleron approach to a solid surface. Such a signal may be used to avoidcollision with a solid surface. The signal provided by a liquid levelsensing circuit can also be used to detect the presence of alignmentfeatures on the system, thereby determining of the position of theliquid handling probe 100 within the system. Determination of theposition of the liquid handling probe 100 relative to alignment featureson the system may be used for automated alignment of the transportcarriage responsible for movement of the liquid handling probe 100. Suchalignment features can be located to perform additional functions, orplaced on the system specifically for purposes of alignment.

In some embodiments, the invention incorporates the low carryover liquidhandling probe 100 described above with the damage-minimizing probemount 200. The carryover minimizing features of these devices arecomplementary, and the combination of the two may provide optimal systemperformance in addition to greatly simplifying the task of installing orreplacing the liquid handling probe 100.

While detailed descriptions of one or more embodiments have been giveabove, various alternatives, modifications, and equivalents will beapparent to those skilled in the art without varying from the spirit ofthe invention. Moreover, except where clearly inappropriate or otherwiseexpressly noted, the features, devices, and/or components of differentembodiments may be substituted and/or combined. Thus, the abovedescription should not be taken as limiting the scope of the invention.One or more elements of one or more embodiments may be combined with oneor more elements of one or more other embodiments without departing fromthe scope if the invention.

1. A system for minimizing collision damage to a liquid handling probeof an automated analyzer, comprising: a probe mount having a channel; aliquid handling probe coupled to the probe mount; the liquid handlingprobe is movable within the channel of the probe mount when the liquidhandling probe makes an unintended contact with an object; a collisiondetection sensor configured to generate a signal when the liquidhandling probe is moved by the unintended contact with the object; and acontroller configured to alter a trajectory of the liquid handling probeafter receiving the signal from the collision detection sensor.
 2. Thesystem of claim 1, wherein the collision detection sensor is aposition-dependent sensor.
 3. The system of claim 1, wherein thecollision detection sensor is an optical sensor.
 4. The system of claim3, wherein the optical sensor is used in combination with a positionalflag, the optical sensor includes an optical path, and the positionalflag is configured to move through the optical path when the liquidhandling probe is moved by the unintended contact with the object. 5.The system of claim 1, further comprising a pliant member, the collisiondetection sensor configured to generate the signal when the pliantmember is distorted, wherein the plaint member is distorted when theliquid handling probe is moved by the unintended contact with theobject.
 6. The system of claim 5, wherein the collision detection sensoris an optical sensor, the optical sensor is used in combination with apositional flag, the optical sensor includes an optical path, and thepositional flag is configured to move through the optical path when thepliant member is distorted.
 7. The system of claim 1, further comprisinga probe guide, the liquid handling probe is mounted to the probe guide,and the probe guide is mounted to the probe mount, and the liquidhandling probe and the probe guide are movable within the channel of theprobe mount when the liquid handling probe makes the unintended contactwith the object.
 8. The system of claim 7, further comprising a pliantmember, the pliant member interposed between the probe mount and theprobe guide, and the collision detection sensor configured to generate asignal when the pliant member is distorted.
 9. The system of claim 1,wherein the liquid handling probe includes a conductive polymer core,the conductive polymer core having a conductive polymer tip, and theconductive polymer tip is configured to serve as a sensing portion forliquid level sensing.
 10. The system of claim 4, further comprising aprobe guide mounted to the probe mount, wherein the optical sensor ismounted on the probe mount, and the positional flag is mounted on theprobe guide.
 11. The system of claim 4, further comprising a probe guidemounted to the probe mount, wherein the optical sensor is mounted on theprobe guide, and the positional flag is mounted on the probe mount. 12.The system of claim 1, wherein the collision detection sensor is a Halleffect sensor.
 13. The system of claim 1, wherein the probe mount isaffixed to a transport carriage system.
 14. The system of claim 13,wherein the controller is configured to alter the trajectory of themounted liquid handling probe by directing the transport carriage systemto halt movement.
 15. The system of claim 13, wherein the controller isconfigured to alter the trajectory of the mounted liquid handling probeby directing the transport carriage system to reverse movement.
 16. Thesystem of claim 1, wherein the system is further configured to notify auser of a collision after receiving the signal from the collisiondetection sensor.
 17. A method for minimizing collision damage to aliquid handling probe of an automated analyzer, comprising the steps of:generating, using a collision detection sensor, a signal when a liquidhandling probe is moved by an unintended contact with an object, whereinthe liquid handling probe and the collision detection sensor are coupledto a probe mount; receiving, using a controller, the signal from thecollision detection sensor; and altering, using the controller, atrajectory of the liquid handling probe after receiving the signal fromthe collision detection sensor.
 18. The method of claim 17, furthercomprising the step of causing a positional flag to move through anoptical path of the collision detection sensor when the liquid handlingprobe is moved by the unintended contact with the object.
 19. The methodof claim 17, wherein a distortion of a pliant member causes thecollision detection sensor to generate the signal, the pliant member isdistorted when the liquid handling probe is moved by the unintendedcontact with the object.
 20. The method of claim 17, further comprisingthe step of notifying a user of a collision after receiving the signalfrom the collision detection sensor.